Although compressed tablets are among the most popular drug dosage forms, some patients, in particular geriatric, pediatric or uncooperative patients, may have difficulties to swallow them. For this reason, orodispersible or orally disintegrating tablets (ODTs) might serve as an alternative dosage form for patients who experience dysphagia. Common among all age groups, dysphagia is observed in about 35% of the general population as well as up to 60% of the elderly institutionalized population.
These problems have been partially addressed by the provision of ODTs that disintegrate in the mouth into smaller pieces allowing easy swallowing. Such tablets need to be strong enough to withstand packaging, transport and subsequent handling without breaking, yet they must be capable of disintegrating gradually when placed into the oral cavity. One regulatory condition explaining what requirements should be met by an ODT is USP method 701 for disintegration. FDA guidance issued in December 2008 stated that ODTs should disintegrate in less than 30 seconds.
Various technologies have been developed that enable the preparation of ODTs, such as spray drying, freeze drying, molding, sublimation, floss formation, direct compression, dry granulation and wet granulation, whereas many of these technologies have proved to be successful only for specific drugs. ODTs are often produced by compressing granules containing at least one active pharmaceutical ingredient (API) together with excipients that trigger dissolving of the tablet in the mouth.
Although a rapid dissolution of the ODT in the oral cavity and absorption through the buccal mucous membrane might be preferred for some APIs, there is a large group of APIs which have an unpleasant taste, smell or cause heartburn or other unfavourable sensation which might lead to a decreased compliance, in particular in pediatric patients. Therefore, coating technologies have been proposed for coating the core components, like granules or pellets, which will be compressed later on to form the final ODT.
WO 2007/036632 corresponding to US 2008/0248111 discloses ODTs of bitter APIs. It is described to use coated granules comprising at least one amine-containing API complexed by low cation-exchange resin and at least one hydrophilic adsorbent, where the mixture of both components is coated with a gastrosoluble polymer. WO 2007/036632 further concerns a method for preparing such granules as well as orodispersible tablets containing such granules. As an example of a gastrosoluble polymer defined as a polymer which dissolves in the stomach at a pH between 1 and 3, Eudragit® E100 is named among others. Furthermore, in one example, it is disclosed to use a mixture of Eudragit® E100 and precipitated silica for coating granules. The weight ratio of the precipitated silica in this coating composition (based on the dry weight of the composition) is about 9.8% by weight. Further, the addition of fatty acids to the coating composition is not disclosed.
EP 1 964 549 A1 further discloses an ODT comprising a fat-soluble API. The ODT is obtained by tableting a mixture of different ingredients adsorbed to an adsorbent. The adsorbent might be selected from the group of calcium silicate, magnesium aluminometasilicate, hydrated silicon dioxide and light anhydrous silicic acid. According to example 1, the weight ratio of hydrated silicone dioxide used is about 55.9% by weight.
EP 1 157 690 concerns a sustained release composition of a core comprising an active ingredient, and a functional coating comprising a gastroresistant polymer and hydrophilic silicon dioxide. A combination of solid fatty acids, silica and a gastro-soluble (meth)acrylate based (co)polymer in the coating is not disclosed.
EP 1 759 692 describes the supply and production of an animal medicine consisting of a substrate in pellet or tablet form, which is attractive to livestock and domestic animals and which consists of yeast or dry animal feed of vegetable or animal origin, in which fine-grained particles of a neutral-tasting, physiologically compatible, solid carrier material are embedded. Said fine-grained particles of carrier material are coated with an active substance for veterinary medicine and said active substance layer is encased with a protective layer of a physiologically compatible polymer matrix. A combination of solid fatty acids, silica and a gastro-soluble (meth)acrylate based (co)polymer in the coating is not disclosed as well.
WO 2010/046933 relates to a pharmaceutical composition of linezolid for oral administration, comprising taste-masked linezolid and at least one pharmaceutically acceptable excipient. The taste-masked linezolid comprises linezolid and at least one taste-masking agent. The pharmaceutical compositions of taste-masked linezolid are suitable for oral administration as suspensions, powders for suspensions, dispersible tablets, orally disintegrating tablets, chewable tablets, effervescent tablets and the like. Combinations of taste-masking coatings comprising solid fatty acids, silica and a gastro-soluble (meth)acrylate based (co)polymer are not disclosed.
WO2008/015220 relates to granules comprising oxycodone, as well as to orally disintegrating tablets including same and optionally acetaminophen. The use of solid fatty acids in a taste-masking coating is not described in this publication.
Generally, in the prior art technologies, hydrated silicas or colloidal silicas were rather used in the formulation of the core component of a pharmaceutical formulation (for example as glidants, as anti-caking agents, as adsorbents) than in coating compositions. Recently, they have been suggested in coating formulations still as anti-caking agents, needed to prevent agglomeration and sticking of the polymer particles during the preparation of the coating dispersion together. Generally, talcum or magnesium stearate are the common choice for these properties.
Silicas may also impact the release behaviour of the pharmaceutical formulation because they influence the formulation's properties such as hydrophilicity, porosity and swallowability. Generally, in the prior art coatings, silicas are intended to increase the drug release from the formulation (see FIG. 8); Advances in Delivery Science and Technology, Controlled Release in Oral Drug Delivery; Clive G. Wilson, Patrick J. Crowley. (2011); Chapter: Coated Multiparticulates for Controlling Drug Release (p. 269). Moreover, the influence of the use of these silica compounds combined with talcum has been barely investigated, especially in the field of controlled release dosage forms.
Solid fatty acids have been frequently used as auxiliaries in prior art formulations. For example, they find application as glidants in the tableting technology. However, due to their lipophilic and hydrophobic nature, they are not used in applications, where an efficient and rapid dissolution is required in body fluids such as gastric juice.